In the field of medical devices, particularly medical devices that are implantable within a subject, predictable and controllable performance is essential to the successful treatment of a patient. An example of an implantable medical device is a stent. Stents can act as a mechanical means to physically hold open and, if desired, expand a passageway within a subject. Typically, a stent is compressed, inserted into a small vessel through a catheter, and then expanded to a larger diameter once placed in a proper location. Stents play an important role in a variety of medical procedures such as, for example, percutaneous transluminal coronary angioplasty (PTCA), a procedure used to treat heart disease by opening a coronary artery blocked by an occlusion. Stents are generally implanted in such procedures to reduce occlusion formation, inhibit thrombosis and restenosis, and maintain patency within vascular lumens. Examples of patents disclosing stents include U.S. Pat. No. 4,733,665 to Palmaz, U.S. Pat. No. 4,800,882 to Gianturco, and U.S. Pat. No. 4,886,062 to Wiktor.
Stents and other medical devices are also being developed to locally deliver active agents, e.g. drugs or other medically beneficial materials. Local delivery is often preferred over systemic delivery, particularly where high systemic doses are necessary to affect a particular site. For example, agent-coated stents have demonstrated dramatic reductions in stent restenosis rates by inhibiting tissue growth associated with restenosis.
Proposed local delivery methods from medical devices include coating the device surface with a layer comprising a polymeric matrix and attaching an active agent to the polymer backbone or incorporating the active agent by dispersing, impregnating or trapping it in the polymeric matrix. For example, one method of applying an active agent to a stent involves blending the agent with a polymer dissolved in a solvent, applying the composition to the surface of the stent, and removing the solvent to leave a polymer matrix in which an active agent is impregnated, dispersed or trapped. Once the medical device, for example a stent, has been implanted at the treatment site, the active agent has a release-rate profile from the polymer matrix that is dependent upon a variety of factors including, for example, the composition of the polymer matrix and the active agent.
It is highly desirable to be able to modulate active-agent release-rates from a polymer matrix to provide the most medically efficacious treatment. For example, in a polymer coating for a stent comprising more than one active agent it may be desirable that one of the active agents have a slower or faster release-rate from the polymer matrix, or to maintain a concentration of one or more of the active agents at a therapeutically effective level for a prolonged period of time. Those skilled in the art will therefore appreciate that local delivery of active agents would benefit not only from improved release-rate profiles that are controllable and predictable, but also from release-rate profiles that can be tailored to the particular medical treatment.
The embodiments of the present invention address such needs, as well as others, by providing methods for modulating and/or controlling the release-rates of active agents from medical devices and coatings for medical devices.